Small-molecule probe reveals a kinase cascade that links stress signaling to TCF/LEF and Wnt responsiveness

被引：5

作者：

Cheng, Jiongjia ^{[1
,9
]}

Tsuda, Masanao ^{[2
]}

Okolotowicz, Karl ^{[1
]}

Dwyer, Mary ^{[1
]}

Bushway, Paul J. ^{[2
,3
]}

Colas, Alexandre R. ^{[2
]}

Lancman, Joseph J. ^{[2
]}

Schade, Dennis ^{[1
,4
]}

Perea-Gil, Isaac ^{[5
]}

Bruyneel, Arne A. N. ^{[5
]}

Lee, Jaechol ^{[5
]}

Vadgama, Nirmal ^{[5
]}

Quach, Justine ^{[1
]}

McKeithan, Wesley L. ^{[2
,5
]}

Biechele, Travis L. ^{[7
]}

Wu, Joseph C. ^{[5
,6
]}

Moon, Randall T. ^{[7
]}

Dong, P. Duc Si ^{[2
]}

Karakikes, Ioannis ^{[5
,8
]}

Cashman, John R. ^{[2
]}

Mercola, Mark ^{[2
,3
,5
,6
]}

机构：

[1] Human BioMol Res Inst, 5310 Eastgate Mall, San Diego, CA 92121 USA

[2] Sanford Burnham Prebys Med Discovery Inst, 10901 North Torrey Pines Rd, La Jolla, CA 92037 USA

[3] Univ Calif San Diego, San Diego, CA 92093 USA

[4] Christian Albrechts Univ Kiel, Inst Pharm, Gutenbergstr 76, Kiel, Germany

[5] Stanford Univ, Cardiovasc Inst, 240 Pasteur Dr, Palo Alto, CA 94305 USA

[6] Stanford Univ, Dept Med, 240 Pasteur Dr, Palo Alto, CA 94305 USA

[7] Univ Washington, Dept Pharmacol, Seattle, WA 98105 USA

[8] Stanford Univ, Dept Cardiothorac Surg, 240 Pasteur Dr, Palo Alto, CA 94305 USA

[9] Nanjing Xiaozhuang Univ, Coll Environm Sci, Nanjing 211171, Peoples R China

来源：

CELL CHEMICAL BIOLOGY | 2021年 / 28卷 / 05期

关键词：

DNA-DAMAGE RESPONSE; BETA-CATENIN; IONIZING-RADIATION; PDZ DOMAIN; STEM-CELLS; PHOSPHORYLATION; INHIBITOR; PATHWAY; ATM; SPINDLE;

D O I：

10.1016/j.chembiol.2021.01.001

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Wnt signaling plays a central role in tissue maintenance and cancer. Wnt activates downstream genes through beta-catenin, which interacts with TCF/LEF transcription factors. Amajor question is how this signaling is coordinated relative to tissue organization and renewal. We used a recently described class of small molecules that binds tubulin to reveal amolecular cascade linking stress signaling through ATM, HIPK2, and p53 to the regulation of TCF/LEF transcriptional activity. These data suggest a mechanism by which mitotic and genotoxic stress can indirectly modulate Wnt responsiveness to exert coherent control over cell shape and renewal. These findings have implications for understanding tissue morphogenesis and small-molecule anticancer therapeutics.

引用

页码：625 / +

页数：16

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